Premium
Activation of Elk‐1 participates as a neuroprotective compensatory mechanism in models of Huntington’s disease
Author(s) -
AngladaHuguet Marta,
Giralt Albert,
PerezNavarro Esther,
Alberch Jordi,
Xifró Xavier
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07711.x
Subject(s) - huntingtin , neuroprotection , huntington's disease , biology , huntingtin protein , striatum , medium spiny neuron , microbiology and biotechnology , neurodegeneration , exon , transcription factor , neuroscience , mutant , medicine , gene , genetics , disease , dopamine
J. Neurochem. (2012) 121 , 639–648. Abstract The transcription factor Elk‐1 has been revealed as neuroprotective against toxic stimuli. In this study, we explored the neuroprotective capacity of Elk‐1 in Huntington’s disease. To this aim, we used two exon‐1 mutant huntingtin (mhtt) mouse models (R6/1 and R6/2), and a full‐length mhtt striatal cell model (STHdh Q111/Q111 ). Analysis of Elk‐1 and pElk‐1 Ser383 in the striatum of R6 mice revealed increased levels during the disease progression. Similarly, Elk‐1 and pElk‐1 Ser383 levels were increased in STHdh Q111/Q111 cells when compared with wild‐type cells. In addition, we observed a predominant nuclear localization of Elk‐1 in STHdh Q111/Q111 cells, and in the striatum of 30‐week‐old R6/1 mice. Nuclear Elk‐1 did not colocalize with mhtt aggregates, suggesting a higher transcriptional activity. In agreement, the knock‐down of Elk‐1 decreased immediate early genes expression in STHdh Q111/Q111 cells, but not in wild‐type cells. Interestingly, reduction of Elk‐1 levels by siRNAs transfection promoted cell death and caspase 3 cleavage in STHdh Q111/Q111 cells, but not in wild‐type cells. In summary, we propose that increased protein levels, phosphorylation and nuclear localization of Elk‐1 observed in exon‐1 and full‐length Huntington’s disease models could be a compensatory mechanism activated by striatal cells in response to the presence of mhtt that contributes to neuroprotection.